Substituted gamma aminobutyric acids as pharmaceutical agents

Abstract

Novel gamma aminobutyric acids of formula (I) are disclosed and are useful as agents in the treatment of epilepsy, faintness attacks, hypokinesia, cranial disorders, neurodegenerative disorders, depression, anxiety, panic, pain, neuropathological disorders, inflammation, and gastrointestinal damage. Processes for the preparation and intermediates useful in the preparation are also disclosed.

What is claimed is: 
     
       1. The compounds of Formula I ##STR16## or a pharmaceutically acceptable salt thereof wherein: R is hydrogen or lower alkyl; R 1  is hydrogen or lower alkyl; ##STR17## straight or branched alkyl of from 8 to 11 carbons, --(CH 2 ).sub.(1-4) --X--(CH 2 ).sub.(0-4) -phenyl,   wherein X is --O--, --S--, --NR 3  -- wherein   R 3  is alkyl of from 1 to 6 carbons, cycloalkyl of from 3 to 8 carbons, benzyl, phenyl,   wherein phenyl and benzyl can be unsubstituted or substituted with from 1 to 3 substituents each independently selected from alkyl, alkoxy, halogen, hydroxy, carboxy, carboalkoxy, trifluoromethyl, amino, and nitro.   
     
     
       2. A compound according to claim 1 wherein R 1  is hydrogen or methyl; and ##STR18##   
     
     
       3. A compound according to claim 1 wherein R 1  is hydrogen or methyl and ##STR19## 
     
     
       4. A compound according to claim 1 wherein R 1  is hydrogen or methyl; and R 2  is (CH 2 ) 1-4  --X--(CH 2 ) 0-4  -phenyl.   
     
     
       5. A compound according to claim 1 wherein R 1  is hydrogen or methyl and   R 2  is (CH 2 ) 1  --S--(CH 2 ) 0-4  -phenyl.   
     
     
       6. A compound according to claim 1 wherein R 1  is hydrogen or methyl; and   R 2  is straight or branched alkyl of from 8 to 11 carbons.   
     
     
       7. A compound according to claim 1 and selected from 3-Aminomethyl-4-cyclohexyl-butyric acid;   3-Aminomethyl-5-phenyl-pentanoic acid;   3-Aminomethyl-5-benzylsulfanyl-pentanoic acid;   3-Aminomethyl-5-(4-bromo-benzylsulfanyl)-pentanoic acid;   3-Aminomethyl-5-(3,4-dichloro-benzylsulfanyl)-pentanoic acid;   5-(4-Amino-benzyloxy)-3-aminomethyl-pentanoic acid;   3-Aminomethyl-5-(4-trifluoromethyl-phenylsulfanyl)-pentanoic acid;   3-Aminomethyl-5-p-tolylsulfanyl-pentanoic acid;   3-Aminomethyl-4-[2-(4-chloro-phenyl)-ethylsulfanyl]-butyric acid;   3-Aminomethyl-4-[2-(2,4-dichloro-phenyl)-ethylsulfanyl]-butyric acid;   3-Aminomethyl-4-(4-methyl-benzylsulfanyl)-butyric acid;   3-Aminomethyl-4-(4-bromo-phenylsulfanyl)-butyric acid;   3-Aminomethyl-4-(3,4-dichloro-benzylsulfanyl)-butyric acid;   3-Aminomethyl-4-cyclobutyl-butyric acid hydrochloride;   3-Aminomethyl-4-cyclopropyl-butyric acid; and   3-Aminomethyl-4-(4-tert-butyl-phenoxy)-butyric acid.   
     
     
       8. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 and a pharmaceutically acceptable carrier. 
     
     
       9. A method for treating epilepsy comprising administering a therapeutically effective amount of a compound according to claim 1 to a mammal in need of said treatment. 
     
     
       10. A method for treating faintness attacks, hypokinesia, and cranial disorders comprising administering a therapeutically effective amount of a compound according to claim 1 to a mammal in need of said treatment. 
     
     
       11. A method for treating neurodegenerative disorders comprising administering a therapeutically effective amount of a compound according to claim 1 to a mammal in need of said treatment. 
     
     
       12. A method for treating depression comprising administering a therapeutically effective amount of a compound according to claim 1 to a mammal in need of said treatment. 
     
     
       13. A method for treating anxiety comprising administering a therapeutically effective amount of a compound according to claim 1 to a mammal in need of said treatment. 
     
     
       14. A method for treating panic comprising administering a therapeutically effective amount of a compound according to claim 1 to a mammal in need of said treatment. 
     
     
       15. A method for treating pain comprising administering a therapeutically effective amount of a compound according to claim 1 to a mammal in need of said treatment. 
     
     
       16. A method for treating neuropathological disorders comprising administering a therapeutically effective amount of a compound according to claim 1 to a mammal in need of said treatment. 
     
     
       17. A method for treating inflammation comprising administering a therapeutically effective amount of a compound according to claim 1 to a mammal in need of said treatment. 
     
     
       18. A method for treating gastrointestinal damage comprising administering a therapeutically effective amount of a compound according to claim 1 to a mammal in need of said treatment.